Research is directed toward understanding the molecular mechanism of pre-neural taste perception. Mammalian taste receptors generally have a weak affinity for their ligands and cannot be used as receptor specific probes. To circumvent this problem compounds are being prepared which can act as site specific irreversible inhibitors. The compounds with the greatest promise in this respect are several epoxy, diazonium and aryl azide derivatives of potent sweet stimuli. A number of commercially available protein modification reagents are also being evaluated as to their effects of taste stimulation in the rat. Affinity labels will be exploited as an experimental tool to investigate receptor topography, receptor-receptor interactions, and as a receptor specific tag for the isolation and characterizaton of taste receptor proteins.